Interpreting a pathogen’s blueprint

Ebola virus inflicts vascular damage that results in fatal bleeding in a majority of infected patients, and remains a near-unstoppable killer. However, a better understanding of the structural and functional roles of Ebola virus proteins could guide the design of effective vaccines and therapeutic agents.

Recent work from an international team led by John Briggs of the European Molecular Biology Laboratory in Heidelberg, Germany, offers some hope, presenting a model for the process by which Ebola virus assembles its nucleocapsid (NC)¹ — the combination of protein and genomic RNA that forms the viral core.

Briggs and colleagues used high-resolution imaging techniques to visualize isolated NC complexes, which assemble into dense helical structures. They subsequently determined that the combination of viral RNA and the viral NP protein is sufficient to initiate the formation of this structure, although subsequent binding by the VP40 protein appears necessary to condense the NC into its proper, compact form. This sets the stage for the final two NC proteins, VP24 and VP35, to bind, locking the NC helix into a rigid state with numerous protein protrusions at regular intervals. These data also reveal likely mechanisms by which these stepwise interactions occur, offering potentially valuable new insights into the process of Ebola virus assembly and maturation.